chr6-35583636-T-A

Variant names:

• chr6-35583636-T-A
• rs7755289
• NM_004117.4:c.840+3398A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001145777.2(FKBP5):​c.*3340A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 927,436 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0044 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (8 hom.)
• Consequence: FKBP5 NM_001145777.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 5 publications found

Genes affected

FKBP5 (HGNC:3721): (FKBP prolyl isomerase 5) The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds to the immunosuppressants FK506 and rapamycin. It is thought to mediate calcineurin inhibition. It also interacts functionally with mature hetero-oligomeric progesterone receptor complexes along with the 90 kDa heat shock protein and P23 protein. This gene has been found to have multiple polyadenylation sites. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

LINC03135 (HGNC:58100):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS2: High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145777.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	NM_004117.4	MANE Select	c.840+3398A>T		intron	N/A	NP_004108.1	Q13451-1
	FKBP5	NM_001145777.2		c.*3340A>T		3_prime_UTR	Exon 7 of 7	NP_001139249.1	Q13451-2
	FKBP5	NM_001145775.3		c.840+3398A>T		intron	N/A	NP_001139247.1	Q13451-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FKBP5	ENST00000357266.9	TSL:1 MANE Select	c.840+3398A>T		intron	N/A	ENSP00000349811.3	Q13451-1
	FKBP5	ENST00000536438.5	TSL:1	c.840+3398A>T		intron	N/A	ENSP00000444810.1	Q13451-1
	FKBP5	ENST00000539068.5	TSL:1	c.840+3398A>T		intron	N/A	ENSP00000441205.1	Q13451-1

Frequencies

GnomAD3 genomes AF: 0.00438 AC: 667 AN: 152164 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00311

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00419

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00402 AC: 3115 AN: 775154 Hom.: 8 Cov.: 11 AF XY: 0.00396 AC XY: 1422 AN XY: 359432

African (AFR) AF: 0.00321 AC: 47 AN: 14642

American (AMR) AF: 0.00434 AC: 4 AN: 922

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 56 AN: 4762

East Asian (EAS) AF: 0.00179 AC: 6 AN: 3348

South Asian (SAS) AF: 0.00236 AC: 36 AN: 15270

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 268

Middle Eastern (MID) AF: 0.0165 AC: 25 AN: 1516

European-Non Finnish (NFE) AF: 0.00398 AC: 2823 AN: 709042

Other (OTH) AF: 0.00465 AC: 118 AN: 25384

GnomAD4 genome AF: 0.00437 AC: 666 AN: 152282 Hom.: 2 Cov.: 32 AF XY: 0.00447 AC XY: 333 AN XY: 74458

African (AFR) AF: 0.00313 AC: 130 AN: 41568

American (AMR) AF: 0.0105 AC: 161 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5186

South Asian (SAS) AF: 0.00208 AC: 10 AN: 4818

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10614

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00418 AC: 284 AN: 68008

Other (OTH) AF: 0.0104 AC: 22 AN: 2112

Alfa AF: 0.00365 Hom.: 0

Bravo AF: 0.00580

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.41
DANN	Benign	0.54
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7755289; hg19: chr6-35551413;